Stem Cell Membrane‐Encapsulated Zeolitic Imidazolate Framework‐8: A Targeted Nano‐Platform for Osteogenic Differentiation

Abstract Mesenchymal stem cells (MSCs) have been recognized as one of the most promising pharmaceutical multipotent cells, and a key step for their wide application is to safely and efficiently regulate their activities. Various methods have been proposed to regulate the directional differentiation of MSCs during tissue regeneration, such as nanoparticles and metal ions. Herein, nanoscale zeolitic imidazolate framework‐8 (ZIF‐8), a Zn‐based metal–organic framework, is modified to direct MSCs toward an osteoblast lineage. Specifically, ZIF‐8 nanoparticles are encapsulated using stem cell membranes (SCMs) to mimic natural molecules and improve the biocompatibility and targeted ability toward MSCs. SCM/ZIF‐8 nanoparticles adjust the sustained release of Zn 2+ , and promote their specific internalization toward MSCs. The internalized SCM/ZIF‐8 nanoparticles show excellent biocompatibility, and increase MSCs’ osteogenic potentials. Moreover, RNA‐sequencing results elucidate that the activated cyclic adenosine 3,5‐monophosphate (cAMP)‐PKA‐CREB signaling pathway can be dominant in accelerating osteogenic differentiation. In vivo, SCM/ZIF‐8 nanoparticles greatly promote the formation of new bone tissue in the femoral bone defect detected by 3D micro‐CT, hematoxylin and eosin staining, and Masson staining after 4 weeks. Overall, the SCM‐derived ZIF‐8 nanostructures achieve the superior targeting ability, biocompatibility, and enhanced osteogenesis, providing a constructive design for tissue repair.